This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The generation, propagation, and modulation of electrical signals in the nervous system require the precise subcellular localization of ion channels in neurons. For example, disrupted ion channel or neurotransmitter receptor distribution or density play important roles in neuropathic pain, spinal cord injury, schizophrenia, myasthenia gravis, epilepsy, and multiple sclerosis. Two of the best examples of ion channel/receptor clustering in the nervous system are found along axons at and near the node of Ranvier (nodes, paranodes, and juxtaparanodes) and the axon initial segment. Ion channels clustered at these sites play key roles in regulating action potential generation and propagation. However, very little is known about the mechanisms regulating localization and retention of proteins at the AIS and nodes of Ranvier. A major impediment to understanding how ion channels are clustered at axon initial segments and nodes of Ranvier is the relatively few numbers of proteins that have been identified at these sites. In this project, we will work to identify new components of nodes, paranodes, juxtaparanodes, and axon initial segments.